The objective of the proposed research is to conduct and evaluate a pilot program for the simultaneous screening of carriers for cystic fibrosis (CF), Tay Sachs disease (TSD), and Gaucher disease (GD) in the Ashkenazi Jewish population. This ethnic group is unique since 95% of CF and GD carriers can be detected, providing the rationale to introduce CF and GD screening in conjunction with Tay-Sachs (TSD) carrier screening programs which have proven acceptability and effectiveness. The program will introducer genetic screening for GD, the most prevalent Jewish genetic disease. This pilot screening study will address issues of education, improved and cost-effective test methods, effective counseling and potential psychologic harm as well as ethical and health policy considerations. Recruitment of 10,000 Ashkenazi Jewish participants ((about 5000 couples) will be facilitated by physician advocacy and articles in Jewish community publications. Couples prior to or early in pregnancy will be screened for TSD, CF and GD; these disorders have "carrier couple" detectabilities of about 99%, 90% and 98%, respectively, using DNA diagnostic and enzyme-based assays. All participants will receive an informational brochure describing the study; the major manifestations, treatment and inheritance of each disease; the testing protocol and follow-up requests. Focus group testing will guide the development of the educational materials. The impact of the materials will be determined by baseline assessment of the participant's knowledge of the three disorders. All carriers will receive results from a genetic counselor by telephone. Questionnaires, administered at the testing session, after reporting results, and then 3 and 12 months later, will assess baseline and retained knowledge of inheritance, major manifestations of CF, TSD and GD; and available treatments for each; attitudes toward screening, family planning and reproductive options; and assessment of anxiety, depression and self-esteem. Psychological studies, within 2 weeks of test results at 3 and 12 months, will assess depression, anxiety, self-esteem, self and societal stigmatization and other areas of concern associated with carrier identification. These studies will investigate the nature and frequency of potential insults to self-esteem and stigmatization associated with carrier identification, and establish guidelines to identify such reactions, and develop a psychological assessment instrument for CF, GD and other carrier screening programs. This pilot program will address issues of health policy related to screening and will include an Ethics/Counseling Oversight Committee, composed of physicians, a genetic counselor, and a medical ethicist, to consider ethical or other patient-related issues. A novel feature of this proposal is that the educational, testing, counseling and psychological follow-up components will be evaluated in Ashkenazi Jewish couples, providing the opportunity to compare the acceptance, knowledge and possible stigmatization for CF and GD with those of TSD, the paradigm for effective testing and counseling of a recessive genetic disease. Moreover, comparison of these diseases will permit identification of screening issues related to differences in disease severity, availability of treatment and detection accuracy for carrier couples.